Efficacy and Safety of BEZ235 Compared to Everolimus in Patients With Advanced Pancreatic Neuroendocrine Tumors

This study has been terminated.
(This trial was terminated based on an interim analysis as BEZ235 did not demonstrate a progression free survival advantage to everolimus treatment.)
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01628913
First received: June 25, 2012
Last updated: March 9, 2016
Last verified: March 2016
  Purpose
This was a multicenter, open label, randomized phase II study to evaluate the efficacy and safety of BEZ235 as compared to everolimus in patients with advanced, low to intermediate grade pancreatic neuroendocrine tumor (pNET).

Condition Intervention Phase
Pancreatic Neuroendocrine Tumors (pNET)
Drug: BEZ235
Drug: Everolimus
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomized Phase II Study of BEZ235 or Everolimus in Advanced Pancreatic Neuroendocrine Tumors

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: up to approx. 18 months ] [ Designated as safety issue: No ]
    PFS is defined as the time from the date of randomization until the date of the first radiologically documented disease progression or death due to any cause. PFS is based on local investigator assessment. Patients will be followed up for the duration of the study and for an expected average of every 12 weeks after randomization. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of all target lesions, or unequivocal progression of non-target lesions, or the appearance of new lesions.


Secondary Outcome Measures:
  • Objective Response Rate [ Time Frame: up to approx. 18 months ] [ Designated as safety issue: No ]
    Proportion of patients with a best overall response during the study of complete response (CR) or partial response (PR), based on the investigator assessment. 2. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for all target and non-target lesions, as well as new lesions as assessed by CT or MRI: Complete Response (CR), Disappearance of all target and non-target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of all target lesions; Overall Response (OR) = CR + PR.

  • Overall Survival (OS) [ Time Frame: up to approx. 30 months ] [ Designated as safety issue: No ]
    Time from randomization to the date of death due to any cause

  • Time to Treatment Failure (TTF) [ Time Frame: up to approx. 18 months ] [ Designated as safety issue: No ]
    Time from randomization to the date of the first of the following events:death due to any cause or progressive disease, treatment discontinuation due to toxicity or treatment discontinuation due to patient preference


Enrollment: 62
Study Start Date: October 2012
Study Completion Date: September 2014
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: BEZ235
Patients received BEZ235 400 mg bid p.o. (by mouth, twice daily)
Drug: BEZ235
BEZ235 400 mg bid p.o. (by mouth, twice daily)
Active Comparator: Everolimus
Patients received Everolimus 10 mg qd p.o. (by mouth, daily)
Drug: Everolimus
Everolimus 10 mg qd p.o. (by mouth, daily)

Detailed Description:
Patients with advanced (unresectable or metastatic), low to intermediate grade (histologically confirmed well and moderately differentiated) pancreatic neuroendocrine tumor (pNET) were randomized to either BEZ235 or everolimus. The study was planned to include 140 patients, with 70 patients in the BEZ235 treatment group and 70 patients in the everolimus treatment group. An interim analysis was conducted on 62 randomized patients. The study was terminated as the BEZ235 treatment did not demonstrate a progression free survival advantage to everolimus treatment.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Advanced histologically confirmed well differentiated pancreatic neuroendocrine tumor
  • Progressive disease within the last 12 months
  • Measurable disease per RECIST Version 1.0 determined by multiphase MRI or triphasic CT

Exclusion Criteria:

  • Prior treatment with mTOR or PI3K inhibitors
  • Patients with more than 2 prior systemic treatment regimens
  • Previous cytotoxic chemotherapy, targeted therapy, or biotherapy within the last 4 weeks

Other protocol-defined inclusion/exclusion criteria may apply

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01628913

Locations
United States, California
Cedars Sinai Medical Center SC-3
Los Angeles, California, United States, 90048
United States, Colorado
University of Colorado Univ Colorado
Aurora, Colorado, United States, 80045
United States, Kentucky
University of Kentucky Univ Kebtucky
Lexington, Kentucky, United States, 40536-0098
United States, New York
Montefiore Medical Center SC
Bronx, New York, United States, 10467
France
Novartis Investigative Site
Lyon, France, 69437
Novartis Investigative Site
Montpellier Cedex 5, France, 34298
Novartis Investigative Site
Paris, France, 75015
Novartis Investigative Site
Reims, France, 51092
Novartis Investigative Site
Toulouse Cedex 4, France, 31054
Italy
Novartis Investigative Site
Bologna, BO, Italy, 40138
Novartis Investigative Site
Pisa, PI, Italy, 56126
Novartis Investigative Site
Roma, RM, Italy, 00189
Netherlands
Novartis Investigative Site
Amsterdam, Netherlands, 1105 AZ
Novartis Investigative Site
Groningen, Netherlands, 9713 GZ
Russian Federation
Novartis Investigative Site
Kazan, Russian Federation, 420029
Spain
Novartis Investigative Site
Sevilla, Andalucia, Spain, 41013
Novartis Investigative Site
Barcelona, Catalunya, Spain, 08035
Novartis Investigative Site
Hospitalet de LLobregat, Catalunya, Spain, 08907
Novartis Investigative Site
Madrid, Spain, 28034
Novartis Investigative Site
Madrid, Spain, 28046
Switzerland
Novartis Investigative Site
Luzern, Switzerland, 6000
United Kingdom
Novartis Investigative Site
Glasgow, United Kingdom, G11 6NT
Novartis Investigative Site
London, United Kingdom, NW3 2QG
Novartis Investigative Site
London, United Kingdom, SE1 9RT
Novartis Investigative Site
Manchester, United Kingdom, M20 9BX
Novartis Investigative Site
Sheffield, United Kingdom, S10 2SJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01628913     History of Changes
Other Study ID Numbers: CBEZ235Z2401  CBEZ235Z2401  2012-000769-19 
Study First Received: June 25, 2012
Results First Received: August 19, 2015
Last Updated: March 9, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Pancreatic
Neuroendocrine tumors
PNET
BEZ235
Everolimus

Additional relevant MeSH terms:
Neuroendocrine Tumors
Carcinoid Tumor
Adenoma, Islet Cell
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Adenoma
Pancreatic Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Everolimus
Sirolimus
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on August 25, 2016